Biological characteristics and clinical treatment of pulmonary sarcomatoid carcinoma: a narrative review

Abstract

Background and objective: Pulmonary sarcomatoid carcinoma (PSC) is a subset of non-small cell lung cancer (NSCLC) with highly malignant, aggressive, and heterogeneous features. Patients with this disease account for approximately 0.1-0.4% of lung cancer cases. The absence of comprehensive summaries on the basic biology and clinical treatments for PSC means there is limited systematic awareness and understanding of this rare disease. This paper provides an overview of the biological characteristics of PSC and systematically summarizes various treatment strategies available for patients with this disease.

Methods: For this narrative review, we have searched literature related to the basic biology and clinical treatment approaches of PSC by searching the PubMed database for articles published from July 16, 1990 to August 29, 2023. The following keywords were used: "pulmonary sarcomatoid carcinoma", "genetic mutations", "immune microenvironment", "hypoxia", "angiogenesis", "overall survival", "surgery", "radiotherapy", "chemotherapy", and "immune checkpoint inhibitors".

Key content and findings: Classical PSC comprises epithelial and sarcomatoid components, with most studies suggesting a common origin. PSC exhibits a higher tumor mutational burden (TMB) and mutation frequency than other types of NSCLC. The tumor microenvironment (TME) of PSC is characterized by hypoxia, hypermetabolism, elevated programmed cell death protein 1/programmed cell death-ligand 1 expression, and high immune cell infiltration. Treatment strategies for advanced PSC are mainly based on traditional NSCLC treatments, but PSC exhibits resistance to chemotherapy and radiotherapy. The advancement of genome sequencing has introduced targeted therapies as an option for mutation-positive PSC cases. Moreover, due to the characteristics of the immune microenvironment of PSC, many patients positively respond to immunotherapy, demonstrating its potential for the management of PSC.

Conclusions: Although several studies have examined and assessed the TME of PSC, these are limited in quantity and quality, presenting challenges for research into the clinical treatment strategies for PSC. With the emergence of new technologies and the advancement of clinical research, for example, savolitinib's clinical study for MET exon 14 skipping mutations positive PSC patients have shown promising outcomes, more in-depth studies on PSC are eagerly anticipated.

Keywords: Pulmonary sarcomatoid carcinoma (PSC); biology; clinical characteristics; treatment strategies.

Figure 1

Comparison of mutation frequencies between PSC and NSCLC. PSC gene mutation frequency is summarized from the reference literature in the Mutation Characteristics section of the main text, with error bars indicating variations in mutation frequency at the same mutation site in PSC across different studies. The data on NSCLC mutation frequency is sourced from the COSMIC database (https://cancer.sanger.ac.uk/cosmic). PSC, pulmonary sarcomatoid carcinoma; NSCLC, non-small cell lung cancer; TP53, tumor protein 53; KRAS, Kirsten rat sarcoma viral oncogene homolog; EGFR, epidermal growth factor receptor; MET, mesenchymal to epithelial transition factor; NF1, neurofibromatosis type 1; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; BRAF, v-Raf murine sarcoma viral oncogene homolog B; COSMIC, catalogue of somatic mutations in cancer database.

Figure 2

Biological characteristics of PSC. (Designed with BioRender). (A) Common origin of different components of PSC, in which EMT plays a key role. (B) PSC exhibits a high TMB. The most common mutations are TP53, KRAS, EGFR, and MET, with the majority of mutations being shared in epithelial and sarcomatoid components. (C) PSC has a high degree of hypoxia, which promotes glycolysis (Glut1 expression increased) and angiogenesis. (D) High levels of immune infiltration and checkpoint expression suggest that PSC is a “hot tumor”. NSCLC, non-small cell lung cancer; EMT, epithelial mesenchymal transition; PSC, pulmonary sarcomatoid carcinoma; TMB, tumor mutational burden; TP53, tumor protein 53; KRAS, Kirsten rat sarcoma viral oncogene homolog; EGFR, epidermal growth factor receptor; MET, mesenchymal to epithelial transition factor; Glut1, glucose transporter 1; PD-1, programmed cell death-1; PD-L1, programmed cell death-ligand 1.

Figure 3

Therapeutic approaches in PSC. (Designed with BioRender). ^!, clinical trial; *, retrospective study; ⁺, database analysis; ^#, case report. The symbols in the left box represent the efficiency of clinical treatment (√√, effective; √, likely effective; ?, controversial). The right side summarizes the clinical treatment strategies for PSC (National Comprehensive Cancer Network Guidelines, 2023) (166). PSC, pulmonary sarcomatoid carcinoma; EGFR, epidermal growth factor receptor; MET, mesenchymal to epithelial transition factor; TKI, tyrosine kinase inhibitor.